{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:45:52Z","timestamp":1789526752052,"version":"build-2803163510"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Infants in neonatal intensive care units (NICUs) are at risk of acquiring organisms with multidrug resistance or high epidemic potential (MDRO+), which may precede invasive infections. High-resolution analysis of transmission cultures of MDRO+ may help mitigate these risks through targeted infection prevention measures.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess the potential of whole-genome sequencing in resolving suspected transmission chains of MDRO+ and to identify associated risk factors for cluster involvement.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective monocentric cohort study was conducted at a level III NICU at the Medical Center\u2013University of Freiburg, Freiburg, Germany. Of 551 admitted infants, 434 were included because they remained on the ward for 48 hours or more and received 1 or more screenings between February 15, 2019, and November 16, 2020. Statistical analysis was conducted from December 1, 2021, to November 10, 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Time-dependent patient- and ward-level factors, medical device use, nursing effort score, invasive procedures, antibiotic use, prevalence of MDRO+, and staffing metrics were analyzed for association with transmission chains.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was transmission of MDRO+, defined as colonization or invasion with genetically indistinguishable bacteria, defined by amplified fragment length polymorphism or whole-genome sequencing. Secondary outcomes included colonization rates, bloodstream infections, and risk factors associated with transmission.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study included 434 infants (median gestational age, 34.6 weeks [IQR, 31.4-38.3 weeks]; 242 boys [55.8%]; median birth weight, 2165 g [IQR, 1410-2965 g]). Overall, 225 patients (51.8% [95% CI, 47.1%-56.5%]) were colonized with at least 1 MDRO+. Of 418 unique colonizations, 142 (34.0% [95% CI, 29.6%-38.6%]) were linked with transmission by whole-genome sequencing. Thirty-seven unique transmission clusters were identified, most frequently involving\n Escherichia coli<\/jats:italic>\n (n\u2009=\u200911). Four of 10 bloodstream infections with MDRO+ (40.0%) were linked with transmission events. Increased full-time nurse staffing (odds ratio [OR], 0.28 [95% CI, 0.21-0.38];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) and prior antibiotic use (OR, 0.41 [95% CI, 0.26-0.63];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001) were associated with decreased transmission risk, while vascular catheter use was associated with increased transmission risk (OR, 1.65 [95% CI, 1.26-2.17];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study involving infants in the NICU suggests that bacterial sequencing can accurately detect bacterial transmission events. Multivariate analysis suggests that the bacterial transmission risk on a NICU can be modified.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.41409","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T16:30:29Z","timestamp":1763742629000},"page":"e2541409","source":"Crossref","is-referenced-by-count":5,"title":["Prospective Whole-Genome Sequencing to Identify Bacterial Transmission and Its Modifiers in Neonates"],"prefix":"10.1001","volume":"8","author":[{"given":"Timmy","family":"Nguyen","sequence":"first","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"B\u00fcrkin","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefany","family":"Ayala-Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Acevedo Monterrosa","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jonas","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Klotz","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center\u2013University of Freiburg, Freiburg, Germany"},{"name":"Bethel Center for Pediatrics, Department of Neonatology and Pediatric Intensive Care, University Hospital OWL, University of Bielefeld, Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schneider","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology and Hygiene, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wolkewitz","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjibbe","family":"Donker","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Reuter","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"G\u00f6tting","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Henneke","sequence":"additional","affiliation":[{"name":"Institute for Infection Prevention and Control, Medical Center\u2013University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"issue":"10","key":"zoi251135r1","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1001\/jamapediatrics.2024.2626","article-title":"Bifidobacterium and Lactobacillus probiotics and gut dysbiosis in preterm infants: the PRIMAL randomized clinical trial.","volume":"178","author":"Van Rossum","year":"2024","journal-title":"JAMA Pediatr"},{"issue":"4","key":"zoi251135r2","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.jhin.2018.03.017","article-title":"Routine screening for colonization by gram-negative bacteria in neonates at intensive care units for the prediction of sepsis: systematic review and meta-analysis.","volume":"99","author":"Seidel","year":"2018","journal-title":"J Hosp Infect"},{"issue":"2","key":"zoi251135r3","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/S0022-3476(78)80523-X","article-title":"Bacterial colonization of neonates admitted to an intensive care environment.","volume":"93","author":"Goldmann","year":"1978","journal-title":"J Pediatr"},{"issue":"1","key":"zoi251135r4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s40168-021-01109-7","article-title":"Bacterial colonization dynamics and antibiotic resistance gene dissemination in the hospital environment after first patient occupancy: a longitudinal metagenetic study.","volume":"9","author":"Klassert","year":"2021","journal-title":"Microbiome"},{"issue":"3","key":"zoi251135r6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cmi.2017.08.008","article-title":"The relationship between gram-negative colonization and bloodstream infections in neonates: a systematic review and meta-analysis.","volume":"24","author":"Folgori","year":"2018","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"zoi251135r7","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1017\/ice.2019.353","article-title":"Length of stay, cost, and mortality of healthcare-acquired bloodstream infections in children and neonates: a systematic review and meta-analysis.","volume":"41","author":"Karagiannidou","year":"2020","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"3","key":"zoi251135r8","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/MPG.0000000000000597","article-title":"Why is initial bacterial colonization of the intestine important to infants\u2019 and children\u2019s health?","volume":"60","author":"Houghteling","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"3","key":"zoi251135r9","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/pr.2017.111","article-title":"The importance of appropriate initial bacterial colonization of the intestine in newborn, child, and adult health.","volume":"82","author":"Walker","year":"2017","journal-title":"Pediatr Res"},{"issue":"3","key":"zoi251135r10","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1093\/jpids\/piw014","article-title":"Colonization with antimicrobial-resistant gram-negative bacilli at neonatal intensive care unit discharge.","volume":"6","author":"Clock","year":"2017","journal-title":"J Pediatric Infect Dis Soc"},{"issue":"1","key":"zoi251135r11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13756-022-01110-1","article-title":"Impact of early antibiotic exposure on the risk of colonization with potential pathogens in very preterm infants: a retrospective cohort analysis.","volume":"11","author":"Bubser","year":"2022","journal-title":"Antimicrob Resist Infect Control"},{"issue":"1","key":"zoi251135r12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13756-021-00901-2","article-title":"Bacterial contamination of neonatal intensive care units: how safe are the neonates?","volume":"10","author":"Bhatta","year":"2021","journal-title":"Antimicrob Resist Infect Control"},{"key":"zoi251135r13","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.1016\/S0378-3782(14)70018-0","article-title":"Management of outbreaks in neonatal intensive care units.","volume":"90","author":"Decembrino","year":"2014","journal-title":"Early Hum Dev"},{"issue":"3","key":"zoi251135r15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.ajic.2006.07.007","article-title":"Outbreaks in neonatal intensive care units\u2014they are not like others.","volume":"35","author":"Gastmeier","year":"2007","journal-title":"Am J Infect Control"},{"key":"zoi251135r16","doi-asserted-by":"publisher","journal-title":"Antimicrobial Stewardship & Healthcare Epidemiology","DOI":"10.1017\/ash.2021.161"},{"issue":"10","key":"zoi251135r18","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s00103-012-1549-5","article-title":"Hygiene measures for infection or colonization with multidrug-resistant gram-negative bacilli. Commission recommendation for hospital hygiene and infection prevention (KRINKO) at the Robert Koch Institute (RKI).","volume":"55","year":"2012","journal-title":"Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz"},{"issue":"9","key":"zoi251135r19","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-034068","article-title":"Protocol for a prospective cohort study: Prevention of Transmissions by Effective Colonisation Tracking in Neonates (PROTECT-Neo).","volume":"10","author":"G\u00f6tting","year":"2020","journal-title":"BMJ Open"},{"issue":"2","key":"zoi251135r22","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/cc6840","article-title":"Competing risks models and time-dependent covariates.","volume":"12","author":"Barnett","year":"2008","journal-title":"Crit Care"},{"key":"zoi251135r24","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2024.1397398","article-title":"Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission.","volume":"12","author":"Jara","year":"2024","journal-title":"Front Pediatr"},{"key":"zoi251135r25","doi-asserted-by":"publisher","year":"2024","journal-title":"Lancet Microbe","DOI":"10.1016\/S2666-5247(23)00290-2"},{"key":"zoi251135r27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13643-015-0131-2","article-title":"Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review.","volume":"4","author":"Wong","year":"2015","journal-title":"Syst Rev"},{"issue":"3","key":"zoi251135r28","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.ajic.2018.08.026","article-title":"Serratia marcescens outbreak in a neonatology unit of a Spanish tertiary hospital: risk factors and control measures.","volume":"47","author":"Redondo-Bravo","year":"2019","journal-title":"Am J Infect Control"},{"issue":"10","key":"zoi251135r29","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00347-23","article-title":"Evaluation of Fourier transform-infrared spectroscopy (FT-IR) as a control measure for nosocomial outbreak investigations.","volume":"61","author":"Uribe","year":"2023","journal-title":"J Clin Microbiol"},{"key":"zoi251135r30","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13756-019-0604-5","article-title":"Amplified fragment length polymorphism and whole genome sequencing: a comparison of methods in the investigation of a nosocomial outbreak with vancomycin resistant enterococci.","volume":"8","author":"Janes","year":"2019","journal-title":"Antimicrob Resist Infect Control"},{"issue":"4","key":"zoi251135r31","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1128\/CMR.00016-17","article-title":"Whole-genome sequencing of bacterial pathogens: the future of nosocomial outbreak analysis.","volume":"30","author":"Quainoo","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"zoi251135r32","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3389\/fcimb.2020.00332","article-title":"Early bacterial colonization and antibiotic resistance gene acquisition in newborns.","volume":"10","author":"Klassert","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"zoi251135r33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/BF01816741","article-title":"Impact of different betalactam antibiotics on the normal human flora, and colonization of the oral cavity, throat and colon.","volume":"10","author":"Heimdahl","year":"1982","journal-title":"Infection"},{"issue":"6","key":"zoi251135r34","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.18831","article-title":"Early antibiotic exposure and bronchopulmonary dysplasia in very preterm infants at low risk of early-onset sepsis.","volume":"7","author":"Shi","year":"2024","journal-title":"JAMA Netw Open"},{"issue":"7","key":"zoi251135r35","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1093\/jac\/dkx088","article-title":"Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.","volume":"72","author":"Esaiassen","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"zoi251135r37","doi-asserted-by":"publisher","first-page":"30427","DOI":"10.1038\/srep30427","article-title":"Screening for gram-negative bacteria: impact of preanalytical parameters.","volume":"6","author":"Warnke","year":"2016","journal-title":"Sci Rep"},{"issue":"1","key":"zoi251135r38","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/j.1539-6924.2006.00863.x","article-title":"Model averaging using fractional polynomials to estimate a safe level of exposure.","volume":"27","author":"Faes","year":"2007","journal-title":"Risk Anal"},{"key":"zoi251135r39","doi-asserted-by":"publisher","first-page":"429","DOI":"10.2307\/2986270","article-title":"Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling.","volume":"43","author":"Royston","year":"1994","journal-title":"Appl Stat"},{"key":"zoi251135r40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/1467-985X.00122","article-title":"Building multivariable prognostic and diagnostic models: transformation of the predictors by using fractional polynomials.","volume":"162","author":"Sauerbrei","year":"1999","journal-title":"J R Stat Soc Ser A Stat Soc"},{"issue":"21","key":"zoi251135r42","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1002\/sim.3940","article-title":"Distributed lag non-linear models.","volume":"29","author":"Gasparrini","year":"2010","journal-title":"Stat Med"},{"key":"zoi251135r23"},{"key":"zoi251135r41","volume-title":"Spline Regression Models: Quantitative Applications in the Social Sciences","author":"Marsh","year":"2001"},{"key":"zoi251135r5","unstructured":"Litz? JE, Goedicke-Fritz? S, H\u00e4rtel? C, Wagenpfeil? G, Zemlin? M, Simon? A. Umsetzung des mikrobiologischen Kolonisationsscreenings: Umfrage an 80 neonatologischen Intensivstationen. Epidemiologisches Bulletin. Robert Koch Institut. September 12, 2019. Accessed September 15, 2025. https:\/\/edoc.rki.de\/bitstream\/handle\/176904\/6269\/37_2019_Artikel.pdf?sequence=1&isAllowed=y"},{"key":"zoi251135r14","unstructured":"Mitteilung der Kommission f\u00fcr Krankenhaushygiene und Infektionspr\u00e4vention (KRINKO). Praktische Umsetzung sowie krankenhaushygienische und infektionspr\u00e4ventive Konsequenzen des mikrobiellen Kolonisationsscreenings bei intensivmedizinisch behandelten Fr\u00fch- und Neugeborenen. Epidemiologisches Bulletin. October 21, 2013. Accessed August 3, 2022. https:\/\/edoc.rki.de\/handle\/176904\/4706?locale-attribute=en"},{"key":"zoi251135r17","unstructured":"Epidemiologisches Bulletin 02\/2012. Robert Koch-Institut. Accessed September 15, 2015. https:\/\/edoc.rki.de\/handle\/176904\/4615"},{"key":"zoi251135r20","unstructured":"Bundesausschuss? G. Beschluss des Gemeinsamen Bundesausschusses \u00fcber eine \u00c4nderung der Qualit\u00e4tssicherungsrichtlinie Fr\u00fch- und Reifgeborene\/QFR-RL: Erstfassung der Datenfelder der Strukturabfrage als Anlage 6. Bundesanzeiger. May 28, 2019. Accessed November 18, 2024. https:\/\/www.g-ba.de\/downloads\/39-261-3581\/2018-11-22_QFR-RL_Erstfassung-Anlage-6_BAnz.pdf"},{"key":"zoi251135r21","unstructured":"Project: PRJEB81699. European Nucleotide Archive. Accessed October 14, 2025. https:\/\/www.ebi.ac.uk\/ena\/browser\/view\/PRJEB81699"},{"key":"zoi251135r26","unstructured":"Artelt? T, Kaase? M, K\u00fcster? H, . INSIST\u2014Impact des Neonatologie-Screenings auf Infektionspr\u00e4diktion \/ Senkung von Transmission. Gemeinsamer Bundesausschuss. 2017. Accessed July 7, 2023. https:\/\/innovationsfonds.g-ba.de\/projekte\/versorgungsforschung\/insist.50"},{"key":"zoi251135r36","unstructured":"INPULS at a glance. Nursing at UKHD. Universit\u00e4ts Klinikum Heidelberg. Accessed October 24, 2024. https:\/\/www.klinikum.uni-heidelberg.de\/organisation\/pflege\/pflegedienst-am-ukhd\/pflegedirektion\/inpulsr\/inpulsr-im-ueberblick-1"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2841748\/nguyen_2025_oi_251135_1763141598.36038.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T16:30:35Z","timestamp":1763742635000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2841748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.41409","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}